tbuckley/cabot-search huggingface dataset:
Management of adjuvant endocrine therapy (AET) side effects in patients with breast cancer: A single cancer center experience.
Authors: Elaine Patricia Kuhn, Jonathan P. Pirruccello, Simon Stone, Tor D Tosteson, Gary N. Schwartz, Mary D. Chamberlin
Journal: Journal of Clinical Oncology (2023)

e12503 Background: Up to 50% of breast cancer survivors are unable to complete the recommended 5-year course of adjuvant endocrine therapy (AET), usually due to side effects. Patients who develop side effects may change to a different medication (‘switch’) or may treat side effects with additional medications or non-pharmacologic strategies. While there are numerous evidence-based treatments available for side effects of AET, the benefit of switching AET is less well known. We have previously reported on the association between switching and early discontinuation of AET. Here, we provide further insight into the use of switching vs side effect management at our cancer center. Methods: We conducted a retrospective chart review of patients diagnosed between 2011-2014 with early stage, ER+/HER2- breast cancer. Clinical data extracted by chart review included side effects and treatment history. Patients were grouped based on whether they received a switch vs side effect management and compared for variables of interest using Chi-squared tests and confidence intervals. Multiple logistic regression was used to assess long-term adherence, adjusting for side effect type and severity. Results: A total of 228 patients with early-stage ER+/HER2- breast cancer were evaluated. Among them, 162 patients (71.0%) received treatment for side effects. A medication switch was offered in 98/162 (60.5%) cases, with side effect management (SEM) alone offered in the remaining (39.5%). Patients who switched were more likely to have reported severe side effects compared to patients who received SEM alone (OR 4.56, 95% CI (2.1, 9.8), p &lt; 0.001). Hot flashes were more frequent in patients who received SEM compared with those switching (89% vs 59%, respectively, p &lt; 0.001), while arthralgias were more frequent in the patients who were offered a switch (70% vs 47%, p = 0.002). ‘Other’ side effects were also more frequent in patients who switched (58% vs 30%, p &lt; 0.001). Among patients who discontinued therapy early, the majority did so within the first 12 months (18/43, 42%). The long-term adherence rate was 73% overall, and it was significantly lower in the subset of patients who received a switch compared to those who received SEM – 62% vs 91% respectively, p &lt; 0.001. Significance was maintained after adjusting for side effect type and severity with multiple logistic regression, p = 0.013. Conclusions: Despite limited evidence, rates of switching are high in clinical practice. Switching is more common in patients with severe symptoms, and those who report arthralgias and uncommon side effects. Switching was associated with poor long-term adherence. Due to the potential for selection bias, conclusions are limited as to whether switching itself is ineffective. A prospective randomized trial is under development at our cancer center to address this question.
The availability of comprehensive care of gastric cancer in developing countries: Georgian experience.
Authors: Tamar Esakia, Mariam Abuladze, Marina Maglakelidze, Khatuna Tsiklauri, Nino Sharikadze, Tamta Cholikidze, Tamari Rukhadze
Journal: Journal of Clinical Oncology (2023)

e13529 Background: The availability of comprehensive cancer care in different regions is the main problem in developing countries. In fact, the cancer centers are centralized and patients fail to receive the proper medical care in regions. The situation is critical for patients living in the zones of conflict. In Georgia we have cancer centers only in two cities Tbilisi and Kutaisi. The aim of the study was to investigate the rate of gastric cancer diagnoses in different regions of Georgia, that could be a model for developing countries. Methods: The spread of gastric cancer in Georgia was investigated retrospectively by analyzing the cases reported in different regions based on 5 years national cancer registry data from 2015 to 2021. The data included the number of cases, age, sex, and stage of gastric cancer. Data from all regions of Georgia were analyzed including occupied regions as Abkhazia and Tskhinvali. Other regions were – Tbilisi, Adjara, Guria, Imereti, Kakheti, Mstkheta, Racha, Samtskhe, Kvemo Kartli, Shida Kartli. Results: A total of 1825 patients with gastric cancer were evaluated during the period of 2015-2021 years. The highest number of diagnosed cases were reported in Tbilisi, with 258 cases in males and 200 cases in females, followed by Imereti (Kutaisi) with 125 cases in males and 80 cases in females and Adjara 132 cases in males and 56 cases in females. The other regions had lower numbers of diagnosed cases, with the lowest being Tskhinvali with only three cases in males and six cases in females. In Abkhazia were 44 cases in males and 19 cases in females. In terms of stage distribution there was no difference between the regions, the majority of patients were stage IV accounting 42 % of all cases, 28% was stage III, 10 % was stage II, 5% was stage I and 15% was of unknown stage. Age ranges were different according to the sex and regions – in Tbilisi 35-83 in males and 26-94 in females, in Adjara 29-88 in males and 28-84 in females, in Abkhazia 35-83 in males and 41-83 in females, in Guria 37-91 in males and 39-83 in females, in Imereti 37-88 in males and 34-84 in females, in Kakheti 34-85 in males and 37-89 in females, in Mtskheta 34-91 in males and 50-84 in females, in Racha 31-72 in males and 30-81 in females, in Samegrelo 33-96 in males and 21-90 in females, in Samtskhe 43-94 in males and 38-81 in females, in Kvemo Kartli 26-85 in males and 38-90 in females, in Shida Kartli 39-85 in males and 38-90 in females, in Tskhinvali 66-84 in males and 33-76 in females. Conclusions: The study found that availability of comprehensive care for gastric cancer including diagnosing is limited in the regions of Georgia, with the lowest rates in occupied regions. To improve the cancer care in developing countries such as Georgia international and national strategies are needed.
Clinical outcomes and correlation with longitudinal circulating tumor (ct)DNA dynamics of a phase I/II study of GSK525762 combined with fulvestrant in patients with hormone receptor-positive/HER2-negative (HR+/HER2−) advanced or metastatic breast cancer.
Authors: David W. Cescon, John Frederick Hilton, Kirsty Hicks, Qu Zhang, Olena Barbash, Arindam Dhar, Mafalda Oliveira, Joseph A. Sparano
Journal: Journal of Clinical Oncology (2023)

1073 Background: Endocrine therapy is the main treatment option for hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2−) metastatic breast cancer (mBC). However, many patients experience disease progression due to resistance to endocrine therapy. Molibresib (GSK525762) is a small-molecule inhibitor of bromodomain and extra-terminal (BET) family proteins (BRD2, BRD3, BRD4, and BRDT). Pre-clinical data suggested that the combination of molibresib with endocrine therapy might overcome endocrine resistance. This study aimed to investigate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy (objective response rate [ORR]) of molibresib combined with fulvestrant in women with HR+/HER2− mBC. The association between early ctDNA dynamics and clinical outcomes was also assessed. Methods: In this phase I/II dose-escalation and expansion study, patients received oral molibresib 60 mg or 80 mg once daily in combination with intramuscular fulvestrant. Patients enrolled had relapsed/refractory, advanced/metastatic HR+/HER2− BC with disease progression on prior treatment with an aromatase inhibitor, with or without a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor. Baseline and week 4 plasma samples were collected and tested using a 74-gene ctDNA panel. Molecular response (MR) was defined as at least 50% reduction of baseline ctDNA level calculated as the average allele frequency of detected single nucleotide variants or indels. Results: The study included 123 patients. The 3 most common molibresib-related adverse events (AEs) were nausea (52%), dysgeusia (49%), and fatigue (44%). At molibresib 60 mg, &gt;90% patients experienced treatment-related AEs, with varying incidence of Grade ≥3 AEs (17%–71%) amongst subgroups. The ORR was 13% (95% confidence interval [CI], 8–20), not meeting the 25% threshold for proceeding to phase II. Among 82 patients with detected baseline circulating tumor DNA, a strong association was observed between baseline copy number amplification (CNA) presence and poor progression-free survival (PFS) with hazard ratio (HR) of 2.89 (95% CI, 1.73–4.83; P &lt; 0.0001). MR was significantly correlated with better PFS (HR=0.38; 95% CI, 0.19–0.75; P = 0.0037), which was further improved when MR was refined as no baseline CNA (HR=0.22; 95% CI, 0.09–0.54; P = 0.0003). Conclusions: Molibresib in combination with fulvestrant did not demonstrate clinically meaningful activity in this study. Copy number adjusted ctDNA MR is a promising early marker for clinical benefit. Clinical trial information: NCT02964507 .
Imbalanced censoring as a bias in evaluation of randomized controlled trials: A simulation-based study.
Authors: Alexey Rumyantsev, Alexandra Tyulyandina, Sergei Tjulandin
Journal: Journal of Clinical Oncology (2023)

e13606 Background: Censoring imbalances between experimental and control arms in clinical trials efficacy can compromise efficacy analysis especially if surrogate endpoints are used. We conducted a simulation-based study to assess the impact of imbalanced censoring in clinical trials on the probability of false-positive outcomes. Methods: With BayesCTDesign R package we created a data set of 500,000 simulated trials. The trials had initially negative results, varying sample sizes (100-2000 patients) and median survival times (1.5-9.5 mo.) with no baseline censoring. Trials with no significant baseline differences (p &gt; 0.2) between experimental and control arms were selected. We randomly censored samples of patients from control (0-20% of sample) and experimental (0-40%) arms for analysis. A logistic regression model was created to assess probability of positive results due to censoring (HR&lt;1 and p value after censoring &lt;0.05). Sample sizes and difference in % of censored subjects were predictors as well as interaction term between these variables. Results: A data set consisting of 399,946 trials was included in the analysis. After random censoring, a statistically significant positive transformation was observed in 61797 trials with corresponding HR&lt;1 (0.59-0.91; p &lt; 0.05) in favor of experimental arm. A logistic regression model with above mentioned variables returned a following equation (p &lt;0.05 for all the variables): y = -6.45005797 + 0.27661437*B 1 + -0.000070584*B 2 + 0.000304167*B 3 where B 0 is the intercept, B 1 – difference in percentage of censored subjects between arms (per %), B 2 – sample size (per subject) and B 3 – an interaction term (B 1 *B 2 ). Pseudo R 2 coefficient was 0.715. Based on the model we estimated a predicted probability of false-positive results for the trials. Conclusions: Clinicians and researchers should pay special attention to censoring imbalances in the clinical trials as these may have a significant impact on results consistency, validity and lead to false-positive findings. [Table: see text]
Metastatic patterns and outcomes by HER2 and hormone receptor (HR) status in patients (pts) with metastatic breast cancer (mBC).
Authors: Qianyu Yuan, Emily Castellanos, Erin Fidyk, Karen Schwed, Melissa Estevez, Sheila Nemeth, Robin Linzmayer, Aaron B. Cohen
Journal: Journal of Clinical Oncology (2023)

1031 Background: HER2-low status in mBC is predictive of benefit to trastuzumab deruxutan, but whether it is biologically distinct from HER2-neg disease is unclear. To better understand the prognostic significance of HER2-low status, we assessed patterns of metastases and real world overall survival (rwOS) by HER2 and HR status. Methods: Pts with mBC diagnosis from 1/1/2011 to 5/31/2022 were selected from the nationwide deidentified Flatiron Health electronic health record (EHR)-derived database. HER2 and HR status was derived from human abstraction (IHC 0-1+/2+/3+, FISH pos/neg, ER/PR) and machine learning-extraction (to classify IHC 0/1+). HER2 and HR tests prior and up to 60 days after metastatic diagnosis date (met Dx date) were included, results closest to met Dx date were used. Sites of metastasis (SOM) were grouped into mutually exclusive groups: brain, non-visceral (bone, skin, lymph node) and visceral (liver, lung, etc). Metastatic patterns stratified by HR/HER2 status were compared using chi-square tests. The association between HER2 status and rwOS, stratified by HR status, was evaluated using Cox models adjusted for age, race/ethnicity, practice, SOM, SES, and stage. rwOS stratified by HR/HER2 status and SOM were estimated via KM analysis. Results: Among 22,932 pts with mBC, HER2-low prevalence was 49%. HER2-low mBC was more likely to be HR+ than HER2-neg or HER2+ (84%, vs 70% and 65%; p&lt;0.01). Pts with HER2-low and HER2-neg mBC had similar SOM overall, distinct from HER2+. For example, among HR+ pts, HER2-low and HER2-neg pts were less likely than HER2+ pts to have brain (4% and 4% vs 10%; p&lt;0.01) or visceral metastases (51%, 50% vs 58%; p&lt;0.01) but more likely to have non-visceral metastases (45% and 46% vs 32%; p&lt;0.01). Compared to HER2-low pts, HER2-neg pts had similar rwOS if HR+ (hazard ratio 1.02, 95% CI 0.98-1.08) and slightly worse if HR-neg (hazard ratio 1.18, 95% CI 1.03-1.21). rwOS varied by HR/HER2 status and SOM. Conclusions: Our findings indicate that HER2-low mBC has biologic similarities to HER2-neg mBC. While slight differences were observed between HER2-neg and HER2-low pts in the HR-neg subgroup, overall rwOS differences were associated more strongly with HER2+ status, HR+ status, and metastatic pattern, indicating that HER2-low status may be more informative as a predictive rather than a prognostic biomarker. [Table: see text]
Oncologic outcomes for different axillary staging techniques in nodal positive breast cancer undergoing neoadjuvant systematic treatment: A cancer registry study.
Authors: André Pfob, Daria Kokh, Irina Surovtsova, Fabian Riedel, Joerg Heil, Philipp Morakis
Journal: Journal of Clinical Oncology (2023)

e12571 Background: The optimal axillary staging technique for patients with nodal positive breast cancer undergoing neoadjuvant systemic treatment (NAST) is unclear. Less invasive, targeted approaches like targeted axillary dissection (TAD) or sentinel-lymph node biopsy (SLNB) recently showed false-negative rates &lt; 10% compared to axillary lymph node dissection (ALND). Oncologic outcomes, however, are unknown. Methods: We identified nodal positive breast cancer patients undergoing NAST from 2016 to 2021 with at least 1-year follow-up and available information regarding axillary staging from the state cancer registry of Baden-Wuerttemberg, Germany. Invasive disease-free survival (iDFS) was assessed using Kaplan-Meier statistics and multivariate cox regression models (adjusted for age, pN stage, pT stage, and tumor biologic subtype). Results: A total of 2403 patients with a median follow-up of 23.2-months after surgery were identified: 1963 underwent ALND, 407 underwent SLNB (in 230 cases, three or more sentinel nodes (SLNs) were removed and in 177 cases, 1-2 SLNs were removed), and 33 underwent TAD. The proportion of patients with pN+ stage within these four groups was 54%, 31%, 26%, and 35%, respectively ( P &lt; 0.001). Significant differences in iDFS between the ALND, SLNB, and TAD groups were observed (log rank P = 0.046): iDFS 2 years after surgery was 74.5% (ALND), 80.2% (SLNB ≥3 removed SLNs), 85.6% (SLNB &lt; 3 removed SLNs), and 88.4% (TAD), respectively. iDFS after 4 years was 61.5% (ALND), 69.1% (SLNB ≥3 removed SLNs), and 74.6% (SLNB &lt; 3 removed SLNs), respectively. Multivariate cox regression analysis showed no significant influence of different axillary staging techniques on iDFS: HR 0.91 (95% CI 0.55 to 1.52) for SLNB with ≥3 removed SLNs, HR 0.99 (95% CI 0.59 to 1.67) for SLNB with &lt; 3 removed SLNs (reference = ALND). Conclusions: This data suggests that ALND provides no benefit in terms of iDFS compared to targeted approaches like TAD or SLNB for patients with nodal positive breast cancer undergoing NAST. Future studies with longer-term follow-up are welcomed to fully inform this discussion.
A phase II randomized clinical trial to assess toxicity and quality of life of patients with breast cancer with hypofractionated versus conventional fractionation radiotherapy with regional nodal irradiation.
Authors: Gabriel Oliveira Bernardes Gil, Warne Pedro Andrade, Paulo Henrique Costa Diniz, Farley Soares Cantidio, Maria Luisa Vieira Gil, Izabella Nobre Queiroz, Conceição Aparecida Mediros Almeida, Paola Palmer Reis Caldeira, Marcos Regalin, Agnaldo Lopes Silva-Filho
Journal: Journal of Clinical Oncology (2023)

588 Background: The primary aim was comparing acute toxicity between conventional fractionated radiation therapy (CF-RT) and hypofractionated radiation therapy (HF-RT) for patients undergoing breast-conserving surgery or mastectomy with breast or chest wall and regional nodal irradiation (RNI). The secondary endpoints were acute and subacute toxicity, cosmesis, quality of life, and lymphedema features. Methods: Unblinded randomized trial with total of 86 patients treated with CF-RT (n = 33; 50 Gy/25 fractions ± sequential boost [10 Gy/5 fractions]) versus HF-RT (n = 53; 40 Gy/15 fractions ± concomitant boost [8 Gy/15 fractions]). Toxic effects and cosmesis evaluation used the Common Terminology Criteria for Adverse Events version 4.03 (CTCAE) and the Harvard/NSABP/RTOG scale. Patients-reported QoL was determined using European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30) and the breast cancer-specific supplementary questionnaire (QLQ-BR23). Lymphedema determination compared volume differences between the affected and contralateral arms using the Casley-Smith volume formula. Results: Grade 2 and grade 3 skin rash dermatitis were lower with HF-RT than with CF-RT (28% vs. 52%, 0% vs. 6%; p = 0.022, respectively). HF-RT vs. CF-RT had lower rate of grade 2 hyperpigmentation (23% vs. 55%; p = 0.005). No differences in overall rates of any physician-assessed grade 2 or higher and grade 3 or higher acute toxicity between HF-RT vs. CF-RT were registered. There was no statistical difference between the CF-RT and the HF-RT regarding cosmesis, lymphedema rate (13% vs. 12% HF-RT vs. CF-RT; p = 1.000, respectively), and functional and symptom scales during irradiation and after six months of treatment. Conclusions: HF-RT showed lower rates of acute toxicity, with no changes in quality-of-life outcomes. Clinical trial information: NCT04015531 .
Rural disparities in telemedicine use among cancer survivors during the COVID-19 pandemic.
Authors: Min Jee Lee, Meng-Han Tsai
Journal: Journal of Clinical Oncology (2023)

e13686 Background: The COVID-19 pandemic has led to significant changes in the delivery of healthcare across the world, including the widespread adoption of telemedicine. This study examined the prevalence of telemedicine use by rurality and determined whether rurality was associated with its use among cancer survivors in the United States (US). Methods: The 2021 National Health Interview Survey (NHIS) was used to examine the use of telemedicine among cancer survivors during the pandemic. Our primary outcome is telemedicine use and rurality is our main exposure of interest. Other covariates of interest include demographics, health-related factors (# of comorbidities, self-rated health), and types of cancer history. Descriptive statistics and multiple logistic regression models were used to examine the mentioned association. Results: Among 27,500 eligible cancer survivors, 51.6% (14,140 participants) of them reported telemedicine use. The use of telemedicine varied by rurality, with 41.4% of rural cancer survivors using telemedicine compared to 58.4% of cancer survivors in large central metropolitan areas (p &lt; 0.001). Rural cancer survivors had significantly lower odds of using telemedicine during the pandemic compared to metropolitan cancer survivors. Cancer survivors residing in rural were 0.58 times less likely (95% CI, 0.43 to 0.78) and cancer survivors residing in medium and small metropolitan areas were 0.72 times less likely (95% CI, 0.56 to 0.93) to report telemedicine use compared to cancer survivors residing in large central metropolitan areas. Conclusions: Significant rural disparities in telemedicine use were evident among cancer survivors. Rural cancer survivors were less likely to use telemedicine during the COVID-19 pandemic. To ensure equitable access to telemedicine, continued reimbursement for telemedicine services, but additional efforts are needed to improve access to and utilization of healthcare for rural cancer survivors.
Association of biophysics-based biomarker with tumor volumetric response in breast cancer treated with immunotherapy.
Authors: Daniel Cook, John R. Pfeiffer, Joseph R. Peterson, Nicole Liadis, Matthew Biancalana, Dorys Lopez, John A. Cole, Anuja K. Antony
Journal: Journal of Clinical Oncology (2023)

608 Background: The treatment landscape of triple negative breast cancer (TNBC) has rapidly changed in recent years, with immuno-oncology (IO) therapies, such as immune checkpoint inhibitors, leading to improvement in patient outcomes. However, the number of patients who benefit is less than 15%, and the therapy itself can prompt severe immune-related adverse events. Breast cancer tumor volume measurements derived from magnetic resonance imaging (MRI) have proven to be a strong predictor of outcome (survival) in patients who either achieve pathological complete response (pCR) or have residual cancer burden (RCB) (ACRIN6657/CALGB150007 I-SPY1). Using an integrative computational approach, we developed both the TumorIO biomarker and the TumorIO Score to predict response to IO therapy in breast cancer patients. Here, we assess the volumetric response in IO-treated patients and its relationship with the TumorIO Score. Methods: We assessed the relationship between breast tumor volumetric response to IO therapy and the TumorIO Score, a previously developed metric that relates probability of IO responsiveness to spatially-resolved tumor biology. We grouped patients into TumorIO Score high vs. low populations, and compared final volumes assessed by MRI and percent response to therapy between groups. Results: We analyzed the volumetric response of IO-treated patients from the I-SPY2 trial and from an independent cohort (total n = 67). Over 96% of the IO-treated patients in the I-SPY2 trial (n = 55) had a greater than 90% volumetric response, while in the independent cohort (n = 12) only 50% of patients had greater than 90% volumetric response. Across both cohorts, 95.8% of patients with a high TumorIO Score achieved &gt; 90% reduction in tumor volume. Additionally, we identified three patients in our cohort that appeared not to respond to IO therapy, who were later classified as progressor, pseudo-progressor, and non-responder patients. The TumorIO biomarker was able to differentiate these three patients, as it associates a unique distinctive biological phenomenon with either response or lack of response. Conclusions: The TumorIO Score provides a novel technology to address several challenges in neoadjuvant IO therapy, namely: predicting which patients are likely to have pCR in response to IO therapy, as well as identifying patients likely to have a substantial volumetric response to IO. Additionally, this method may facilitate subcategorizing patients likely to show radiological pseudo-progression prior to IO administration, although a larger cohort is needed to validate these findings.